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Clinical pharmacology
Cardiotoxic drugs: clinical monitoring and decision making
  1. Audrey H Wu
  1. Dr Audrey H Wu, University of Michigan Health Systems, Cardiovascular Center, SPC 5853, 1500 E Medical Center Drive, Ann Arbor, MI 48109-5853, USA; ahwu{at}med.umich.edu

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Through a variety of mechanisms, the heart is a target of injury for many drugs, both medically prescribed and not. Drugs with potential cardiac toxicity are particularly prominent in cancer treatment, and as survival of cancer patients continues to improve, drug toxicities feature more importantly in long term patient outcomes. This review will focus on intermediate and long term complications (in particular those related to cancer therapy), or acute effects related to drug toxicity (in particular those related to drugs of abuse), with emphasis on those toxicities that can be monitored and/or have specific treatment options. This review will not cover in detail acute complications of chemotherapeutic agents, which are typically transient and occur only during or shortly after drug administration, or toxicities related to overdose of cardiovascular drugs. Finally, note is made regarding epidemiologic associations between specific drugs and adverse cardiovascular outcomes.

COMPLICATIONS OF THERAPIES RELATED TO CANCER TREATMENT

Anthracyclines

The anthracyclines are used to treat a wide range of haematologic and solid malignancies, and are probably the most commonly recognised type of chemotherapy with known cardiac toxicity. Various approaches have been undertaken to reduce drug cardiotoxicity, including structural modifications to the doxorubicin molecule (epirubicin), incorporation into liposomes (doxorubicin, daunorubicin), or development of structurally related drugs (mitoxantrone).1 Long term cardiac toxicity manifests as ventricular dysfunction and clinical heart failure, and is thought to be due to direct myocardial injury from free radicals. Risk of heart failure is most directly related to cumulative dose and administration schedule. The risk of cardiomyopathy increases significantly at cumulative doses >550 mg/m2 although cardiomyopathy can still occur at lower doses. Although the reported incidence of heart failure in modern adjuvant anthracycline therapy trials is 2% or less, recent studies have reported up to 10–50% occurrence of subclinical decline in left ventricular function >10 percentage points after anthracycline treatment.2

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